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      Generation and Applications of Human Pluripotent Stem Cells Induced into Neural Lineages and Neural Tissues

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          Abstract

          Human pluripotent stem cells (hPSCs) represent a new and exciting field in modern medicine, now the focus of many researchers and media outlets. The hype is well-earned because of the potential of stem cells to contribute to disease modeling, drug screening, and even therapeutic approaches. In this review, we focus first on neural differentiation of these cells. In a second part we compare the various cell types available and their advantages for in vitro modeling. Then we provide a “state-of-the-art” report about two major biomedical applications: (1) the drug and toxicity screening and (2) the neural tissue replacement. Finally, we made an overview about current biomedical research using differentiated hPSCs.

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          Most cited references 115

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          Induction of pluripotent stem cells from adult human fibroblasts by defined factors.

          Successful reprogramming of differentiated human somatic cells into a pluripotent state would allow creation of patient- and disease-specific stem cells. We previously reported generation of induced pluripotent stem (iPS) cells, capable of germline transmission, from mouse somatic cells by transduction of four defined transcription factors. Here, we demonstrate the generation of iPS cells from adult human dermal fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc. Human iPS cells were similar to human embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, and telomerase activity. Furthermore, these cells could differentiate into cell types of the three germ layers in vitro and in teratomas. These findings demonstrate that iPS cells can be generated from adult human fibroblasts.
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            Induced pluripotent stem cell lines derived from human somatic cells.

            Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells. These induced pluripotent human stem cells have normal karyotypes, express telomerase activity, express cell surface markers and genes that characterize human ES cells, and maintain the developmental potential to differentiate into advanced derivatives of all three primary germ layers. Such induced pluripotent human cell lines should be useful in the production of new disease models and in drug development, as well as for applications in transplantation medicine, once technical limitations (for example, mutation through viral integration) are eliminated.
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              Embryonic stem cell lines derived from human blastocysts.

              Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages. After undifferentiated proliferation in vitro for 4 to 5 months, these cells still maintained the developmental potential to form trophoblast and derivatives of all three embryonic germ layers, including gut epithelium (endoderm); cartilage, bone, smooth muscle, and striated muscle (mesoderm); and neural epithelium, embryonic ganglia, and stratified squamous epithelium (ectoderm). These cell lines should be useful in human developmental biology, drug discovery, and transplantation medicine.
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                Author and article information

                Journal
                Front Physiol
                Front Physiol
                Front. Physio.
                Frontiers in Physiology
                Frontiers Research Foundation
                1664-042X
                01 January 2012
                19 March 2012
                2012
                : 3
                Affiliations
                1simpleDepartment of Pathology and Immunology, Faculty of Medicine, University of Geneva Geneva, Switzerland
                Author notes

                Edited by: Anis Feki, Geneva University Hospitals, Switzerland

                Reviewed by: Mohammad K. Hajihosseini, University of East Anglia, UK; Petros Papagerakis, University of Michigan, USA

                *Correspondence: Y. Martinez, Department of Pathology and Immunology, University of Geneva, Faculty of Medicine, 1 Rue Michel-Servet, 1206 Geneva, Switzerland. e-mail: yannick.martinez@ 123456unige.ch

                This article was submitted to Frontiers in Craniofacial Biology, a specialty of Frontiers in Physiology.

                Article
                10.3389/fphys.2012.00047
                3307166
                22457650
                Copyright © 2012 Martinez, Dubois-Dauphin and Krause.

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.

                Page count
                Figures: 2, Tables: 3, Equations: 0, References: 111, Pages: 9, Words: 9219
                Categories
                Physiology
                Review Article

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